Abstract 3646: A Novel Therapeutic Program of Exercise after Administration of Lipo-PGE1 and Heparin for Patients with Non Option Peripheral Arterial Disease

BACKGROUND: A program combining heparin administration with exercise is a useful therapeutic strategy for stimulation of collateral development in ischemic legs in patients with non-option peripheral arterial disease (PAD) via transient increase in hepatocyte growth factor. The aim was to examine a hypothesis that additional combination of lipo-prostaglandin (PG) E1, a potent vasodilator and inhibitor of platelet aggregation, accelerates the effectiveness of heparin + exercise program in patients with non-option PAD. METHODS: Study patients were 20 symptomatic PAD (Fontaine II or III) patients who were not candidates for surgical or nonsurgical revascularization because of the lack of distal target vessels or other reasons such as high surgical risk. The patients were randomly assigned in a double blind fashion to two groups; a group of lipo-PGE1(+) (supervised walking for 60 min/day after intravenous administration of 3,000 units heparin and 10 μg lipo-PGE1 for 14 days, n=10) and a group of lipo-PGE1(−) (same supervised walking program after administration of heparin and saline, n=10). After 14-day-initial treatment, the patients of both groups did ambulatory exercise under supervision for 60 min once a day, 3 days/week during a period of following 22 weeks. Ankle brachial pressure index (ABI) and Treadmill test (2.5 km/h, 12% slope) were done before, 2 weeks, 12 weeks, and 24 weeks after the start of program. Ophthalmic examinations and digital subtraction angiography of lower extremities were repeated before and at 24 weeks. RESULTS: Maximum walking time in Treadmill test significantly increased in the group of lipo-PGE1(+) compared with the group of lipo-PGE1(−) at 2 weeks (7.0 ± 2.4 min, 4.8 ± 1.8 min, respectively, P<0.05) but not at 12 weeks (9.2 ± 3.2 min, 7.4 ± 3.1 min, ns) or 24 weeks(10.1 ± 3.6 min, 7.9 ± 3.2 min, ns). There was no significant difference in ABI between two groups through the study period. There were no patients who showed pathological retinal angiogenesis at 24 weeks. CONCLUSION: Additional administration of lipo-PGE1 on heparin + exercise program brings the therapeutic gain appearance forward. This beneficial short-term effect may encourage patients with non-option PAD to maintain exercise training.